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D B Brettler A D Forsberg F D O'Connell A I Cederbaum A K Chaitman P H Levine 《American journal of hematology》1985,18(1):13-18
Because there is little available data to demonstrate whether demand therapy is adequate to prevent progression of hemophilic arthropathy, a cohort of 64 patients with severe Hemophilia A (Factor VIII level less than 1%) and no inhibitor were studied with respect to the progression of knee arthropathy over a period of 6 years. Both degree of disease in flexion and extension and progression of disease were rated on an arbitrary scale. At the outset of the study, the majority of knees were either not restricted or mildly restricted as to motion. Of those knees that were not restricted at the outset, 96% remained not restricted. Of the knees that were mildly restricted, only 58% remained stable or improved over the 6 years, and of the knees that were moderately to severely restricted, 75% improved or remained stable. It thus appears that a demand therapy program can maintain normal range of motion in a knee joint. However, if the patient's joint has progressed to mild disease, the ability to maintain or improve the joint with demand therapy appears to be decreased. 相似文献
23.
Greenough TC Brettler DB Kirchhoff F Alexander L Desrosiers RC O'Brien SJ Somasundaran M Luzuriaga K Sullivan JL 《The Journal of infectious diseases》1999,180(6):1790-1802
Seven long-term nonprogressors (LTNPs) have been identified in a cohort of 128 human immunodeficiency virus (HIV)-1 infected individuals with hemophilia. Studies included quantitation of virus by polymerase chain reaction, characterization of primary virus isolates in vitro, analysis of lymphocyte surface markers, and measurement of virus-specific cytotoxic T lymphocytes (CTLs). Viruses of LTNPs exhibited slow growth in vivo and in vitro. LTNPs had expansion of CD8 T cells with increased expression of HLA-DR. Intermittent HIV-1-specific CTL effector activity was detected in freshly isolated peripheral blood mononuclear cells of most LTNPs. CTL precursor frequencies were higher in LTNPs than in patients with progressive disease. Virus antigen-specific lymphoproliferation was vigorous in some LTNPs. Thus, LTNPs in this cohort have maintained remarkably low virus burdens and vigorous HIV-1-specific cell-mediated immunity over a 15-year period. The presence of expanded, activated CD8 T cells with cytotoxic effector function in the peripheral blood suggests ongoing viral replication. 相似文献
24.
Conventional clotting factor concentrates have, until recently, been "of intermediate purity," containing less than 1% of the coagulation factor, and greater than 99% extraneous plasma proteins such as fibrinogen, fibronectin, gamma globulins, and traces of many others. We report here the results of a new factor VIII concentrate that is purified from human plasma using a mouse monoclonal antibody to factor VIII:vWF in an affinity chromatography system. The resultant concentrate has an activity of between 3,000 and 5,000 U/mg protein before albumin is added as a stabilizer. Seven patients with severe hemophilia A and no inhibitor who were positive for antibody to human immunodeficiency virus (HIV) have been treated solely with this concentrate for over 24 months. Factor usage in these patients has ranged from 611 U/kg/yr to 2,022 U/kg/yr. These patients have infused approximately once per week on the average, most often for joint hemorrhages. The efficacy of the concentrate is excellent. No allergic reactions have occurred and no factor VIII antibodies have developed. In these seven patients mean CD4 counts stabilized (856 +/- 619 at screen v 778 +/- 686 at 24 months) and there was reversal of skin test anergy. In a comparison group on conventional intermediate purity concentrate chosen retrospectively decreases in mean CD4 cell counts similarly did not occur. However, the number of the comparison patients who were anergic increased over the course of the study. These observations indicate the possibility that more highly purified concentrates may stabilize immune function in HIV seropositive patients. 相似文献
25.
26.
Brettler SC Baker JF 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2003,149(2):167-173
The pitch vertical vestibulo-ocular reflex (VOR) is accurate and symmetrical when tested in the normal upright posture, where
otolith organ and central velocity storage signals supplement the basic VOR mediated by the semicircular canals. However,
when the animal and rotation axis are together repositioned by rolling 90° to one side, head forward pitch rotations that
excite the anterior semicircular canals elicit a more accurately timed VOR than do oppositely directed rotations that excite
the posterior canals. This suggests that velocity storage of posterior canal signals is lost when the head is placed on its
side. We recorded from 47 VOR relay neurons, second-order vestibulo-ocular neurons, of alert cats to test whether asymmetries
are evident in the responses of neurons in the medial and superior vestibular nuclei during earth-horizontal axis rotations
in the normal upright posture. Neurons were identified by antidromic responses to oculomotor nucleus stimulation and orthodromic
responses to labyrinth stimulation, and were classified as having primarily anterior, posterior, or horizontal canal input
based on response directionality. Neuronal response gains and phases were recorded during 0.5 Hz and 0.05 Hz sinusoidal oscillations
in darkness. During 0.5 Hz rotations, anterior canal second-order vestibulo-ocular neurons responded approximately in phase
with head velocity (mean phase re head position, ±SE, 80°±3°, n=18), as did posterior canal second-order vestibulo-ocular neurons (mean phase 81°±1°, n=25). Lowering the rotation frequency to 0.05 Hz resulted in only slight advances in response phases of individual anterior
canal second-order vestibulo-ocular neurons (mean phase 86°±6°, mean advance 7°±5°, n=12). In contrast, posterior canal second-order vestibulo-ocular neurons behaved more like semicircular canal afferents, with
responses markedly phase-advanced (mean advance 28°±5°, n=14) by lowering rotation frequency to 0.05 Hz (mean phase 111°±5°, n=14). In summary, low frequency responses of anterior and posterior canal second-order vestibulo-ocular neurons recorded during
horizontal axis pitch correspond to the VOR they excite during vertical axis pitch. These results show that velocity storage
is evident at anterior but not posterior canal second-order vestibulo-ocular neurons. We conclude that responses of posterior
canal second-order vestibulo-ocular neurons are insufficient to explain the accurate low frequency VOR phase observed during
backward head pitch in the upright posture, and that velocity storage or otolith signals required for VOR accuracy are carried
by other neurons.
Electronic Publication 相似文献
27.
J. M. Soucie J. Symons IV B. Evatt D. Brettler H. Huszti J. Linden & THE HEMOPHILIA SURVEILLANCE SYSTEM PROJECT INVESTIGATORS 《Haemophilia》2001,7(2):198-206
Information from the medical records of 2650 US males with haemophilia living in six states was used to examine the influence of infusing factor concentrate at home (home therapy) and other variables on rates of hospitalization for a haemorrhagic bleeding complication (HBC) over a 4-year period. Bleeding complications included actual and suspected haemorrhagic events but excluded elective admissions for procedures necessitated by haemorrhage (e.g. joint synovectomy). Other risk determinants considered in the analyses included age, race, employment status, health insurance type, care received in federally funded haemophilia treatment centres (HTCs), factor deficiency type and severity, amount of factor prescribed, prophylactic treatment, and presence of inhibitors at baseline. Survival analysis methods were used to evaluate relationships between baseline risk factors and subsequent hospitalization rates. During 8708 person years (PYs) of follow-up, 808 subjects (30.5%) had a total of 1847 bleeding-related hospitalizations; an overall rate of 21.2 admissions per 100 PYs. Using proportional hazards regression to adjust for all of the studied factors, we found that home therapy use (among residents of four of the states) and care in HTCs were independently associated with a decreased risk for a first HBC. Patients who had government-sponsored health insurance or who had no insurance, those of minority race or ethnicity, those with higher levels of factor use, and those with inhibitors were at increased HBC risk. We conclude that the use of home therapy and receipt of care in HTCs are each associated with a substantially lower risk for HBC among males with haemophilia. 相似文献
28.
M Colombo P M Mannucci D B Brettler A Girolami E C Lian F Rodeghiero I Scharrer P S Smith G C White 《American journal of hematology》1991,37(4):243-246
A questionnaire-based survey involving 11,801 hemophiliacs from 54 hemophilia centers in the USA and Europe documented the occurrence of hepatocellular carcinoma (HCC) in 10 patients. The crude rate of HCC was 3.2/100,000 patients/year, at least 30 times higher than the background incidence of this tumor in the countries of origin of the patients. All patients were Caucasians with hemophilia A, 39 to 74 years of age, and had liver cirrhosis. All had one or more risk factor for cirrhosis and HCC: 5 were positive for serum hepatitis B surface antigen, 4 had the antibody to hepatitis C virus, and 4 had histories of alcohol abuse. Serum alpha-fetoprotein, measured in 6 patients, was significantly elevated in 4 (range: 807-1399 ng/ml), and only moderately elevated in 2 (25 and 171 ng/ml). The onset of HCC was asymptomatic in 5 patients, whereas it was accompanied by jaundice, abdominal pain, or ascites in the remaining patients. Thus, HCC seems to be a more important secondary disease for hemophiliacs than formerly recognized. Since HCC is often asymptomatic, screening hemophiliacs with chronic liver disease with periodic ultrasound scans might increase the changes of detecting HCC at a stage amenable to surgical treatment. 相似文献
29.
30.
Limiting dilution analysis of cytotoxic T lymphocytes to human immunodeficiency virus gag antigens in infected persons: in vitro quantitation of effector cell populations with p17 and p24 specificities 总被引:2,自引:1,他引:2
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R A Koup C A Pikora K Luzuriaga D B Brettler E S Day G P Mazzara J L Sullivan 《The Journal of experimental medicine》1991,174(6):1593-1600
The presence of cytotoxic T lymphocytes (CTL) to the gag antigens of human immunodeficiency virus (HIV) has been described in infected populations. We found that the majority of this immune response as measured in bulk CTL assays of unstimulated peripheral blood mononuclear cells (PBMC) is directed against the p24 component of the p55 gag precursor protein. Using limiting dilution analysis of this effector cell population we confirm that the majority of activated gag-specific CTL circulating in the PBMC of infected hemophilic patients are directed at p24 determinants and are present at frequencies of 1/36,000 to 1/86,000 lymphocytes. By performing in vitro stimulation after limiting dilution, the precursor population of gag-specific CTL are characterized and quantitated. HIV gag-specific CTL precursors are identified at frequencies of 1/1700 to 1/17,000 lymphocytes and are made up of cells with both p17 and p24 specificities. No HIV gag-specific CTL precursor cells are identified in the PBMC of HIV-uninfected individuals. These studies demonstrate that CTL directed at both p17 and p24 determinants make up the cellular immune repertoire in HIV-infected individuals but that only the p24-specific CTL are routinely found in an activated state in the circulation. 相似文献